Injectable phase-separated tetra-armed poly(ethylene glycol) hydrogel scaffold allows sustained release of growth factors to enhance the repair of critical bone defects.

With the rising prevalence of bone-related injuries, it is crucial to improve treatments for fractures and defects. Tissue engineering offers a promising solution in the form of injectable hydrogel scaffolds that can sustain the release of growth factors like bone morphogenetic protein-2 (BMP-2) for bone repair. Recently, we discovered that tetra-PEG hydrogels (Tetra gels) undergo gel-gel phase separation (GGPS) at low polymer content, resulting in hydrophobicity and tissue affinity. In this work, we examined the potential of a newer class of gel, the oligo-tetra-PEG gel (Oligo gel), as a growth factor-releasing scaffold. We investigated the extent of GGPS occurring in the two gels and assessed their ability to sustain BMP-2 release and osteogenic potential in a mouse calvarial defect model. The Oligo gel underwent a greater degree of GGPS than the Tetra gel, exhibiting higher turbidity, hydrophobicity, and pore formation. The Oligo gel demonstrated sustained protein or growth factor release over a 21-day period from protein release kinetics and osteogenic cell differentiation studies. Finally, BMP-2-loaded Oligo gels achieved complete regeneration of critical-sized calvarial defects within 28 days, significantly outperforming Tetra gels. The easy formulation, injectability, and capacity for sustained release makes the Oligo gel a promising candidate therapeutic biomaterial.

A surface-grafted hydrogel demonstrating thermoresponsive adhesive strength change.

Here, we designed a surface-grafted hydrogel (SG gel) that exhibits thermoresponsive changes in surface properties. Quantitative measurements using a self-made device showed that the adhesive strength between the SG gel surface and a Bakelite plate due to hydrophobic interaction changed significantly with temperature.

Fabrication of Self-Oscillating Gels by Polymer Crosslinking Method and Analysis on Their Autonomous Swelling-Deswelling Behaviors.

We have developed a new methodology for fabricating self-oscillating gels by a post-polymerization crosslinking. The method enables us to make the self-oscillating gels easily just by mixing two kinds of polymer solutions at room temperature with fast gelation. Moreover, the polymer crosslinking method has the advantage that the self-oscillating gels could be fabricated from well-defined linear polymers. We revealed that the dynamic swelling-deswelling behavior of the gels was simply affected by the net amount of the catalyst for the Belousov-Zhabotinsky reaction in the whole gels, although the equilibrium swelling behavior was influenced by the properties of the constituent linear polymers. Our results offer the opportunity to access the origin of the dynamic and equilibrium behavior of materials by the hierarchical assembly as well as enable easy microfabrication of the self-oscillating gel.

Autonomous Nanoscale Chemomechanical Oscillation on the Self-Oscillating Polymer Brush Surface by Precise Control of Graft Density.

As a novel functional surface, a self-oscillating polymer brush that undergoes autonomous, periodic swelling/deswelling during the Belousov-Zhabotinsky (BZ) reaction has been developed. Although extensive research has revealed how the fundamental aspects of the BZ reaction can be regulated based on the surface design of the self-oscillating polymer brush, design strategies for the induction of mechanical oscillation remain unexplored. Herein, we investigated the graft density effects on the phase transition behavior, which is an important design parameter for the mechanical oscillation of the modified polymer. The self-oscillating polymer-modified substrates with controlled graft densities were prepared by immobilizing various compositions of an initiator and a noninitiator followed by surface-initiated atom transfer radical polymerization of the self-oscillating polymer chains. In addition to the characterization of each prepared substrate, atomic force microscopy (AFM) and digital holographic microscopy (DHM) were employed to evaluate the density effects on the static and dynamic surface structures. AFM revealed that equilibrium swelling as well as thermoresponsive behavior is profoundly affected by the graft density. Moreover, using DHM, autonomous mechanical oscillation was captured only on the self-oscillating polymer brush with adequate graft density. Notably, the oscillation amplitude (150 nm) and the period (20 s) in this study were superior to those in a previous report on the self-oscillating polymer modified through the grafting-to method by 10- and 3-fold, respectively. This study presents design guidelines for future applications, such as autonomous transport devices.

Reactivity Control of Polymer Functional Groups by Altering the Structure of Thermoresponsive Triblock Copolymers.

A thermoresponsive ABA triblock copolymer bearing an aldehyde group on the thermoresponsive A segments was synthesized. The polymer formed a micellar assembly due to the hydrophobic interactions of the thermoresponsive segment above the lower critical solution temperature (LCST). In contrast, the ABA polymer assembly decomposed upon lowering the temperature below the LCST. Using this structural change, the reactivity of the aldehyde group toward primary amines of albumin and poly(allylamine) was investigated. When the ABA polymer assembly and reactant were mixed above the LCST, Schiff base formation was suppressed because of the aldehyde group being protected by the hydrophobic thermoresponsive core. In contrast, Schiff base formation between the ABA triblock copolymer and the primary amine moiety on the molecules was confirmed below the LCST. The reactivity of the aldehyde functional group can therefore be controlled by altering the structure of the thermoresponsive ABA polymer.

Precisely Tunable Sol-Gel Transition Temperature by Blending Thermoresponsive ABC Triblock Terpolymers.

Here, we report a facile methodology to control the sol-gel transition temperature (Tgel) of a physically cross-linked hydrogel by blending two kinds of ABC triblock terpolymers. Well-defined triblock terpolymers including thermosensitive N-isopropylacrylamide (NIPAAm), ABC1, and ABC2, were prepared by sequential reversible addition-fragmentation chain transfer polymerization. The chemical structure as well as the molecular weight of the A and B blocks for both polymers are identical, whereas the C blocks are different. The C block of ABC1 (C1) is a statistical copolymer of NIPAAm with hydrophobic n-butyl acrylate (BA), while that of ABC2 (C2) is a PNIPAAm homopolymer. Independently prepared ABC triblock terpolymer solutions exhibit well-defined sol-gel transitions. The Tgel of ABC1 is lower than that of ABC2 since hydrophobic BA is copolymerized into block C1. Remarkably, the Tgel varies linearly within this temperature range by simply blending the two polymers, while the resultant gel strength (∼G') remains almost unchanged. Therefore, the Tgel can be precisely adjusted by the mixing ratio of the two polymers. This method for straightforward manipulation of Tgel has great potential for various soft material applications such as biomaterials for tissue engineering, drug delivery systems, and injectable gels.